open access

Vol 50, No 2 (2012)
ORIGINAL PAPERS
Submitted: 2012-07-04
Accepted: 2012-07-04
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The effect of tyrphostins AG494 and AG1478 on the autocrine growth regulation of A549 and DU145 cells

Agnieszka Bojko, Kinga Reichert, Anna Adamczyk, Joanna Ligęza, Janusz Ligęza, Andrzej Klein
DOI: 10.5603/FHC.2012.0028
·
Folia Histochem Cytobiol 2012;50(2):186-195.

open access

Vol 50, No 2 (2012)
ORIGINAL PAPERS
Submitted: 2012-07-04
Accepted: 2012-07-04

Abstract

We employed two selective EGFR tyrosine kinase inhibitors: AG494 (reversible) and AG1478 (irreversible) for growth regulation of human lung (A549) and prostate (DU145) cancer cell lines, cultured in chemically defined DMEM/F12 medium. Both tested tyrphostins significantly inhibited autocrine growth of the investigated cell lines. The action of AG494 was dose dependent, and at highest concentrations led to complete inhibition of growth. AG1478 seemed to be more effective at lower concentrations, but was unable to completely inhibit growth of A549 cells. Inhibition of EGFR kinase activity by AG494 in contrast to AG1478 had no effect on the activity of ERK in both cell lines. Both EGFR’s inhibitors induced apoptosis of the investigated lung and prostate cancer cell lines, but the proapoptotic effect of the investigated tyrphostins was greater in A549 than in DU145 cells. The tyrphostins arrested cell growth of DU145 and A549 cells in the G1 phase, similarly to other known inhibitors of EGFR. The influence of AG494 and AG1478 on the activity of two signaling proteins (AKT and ERK) was dependent upon the kind of investigated cells. In the case of DU145 cells, there was an evident decline in enzymatic activity of both kinases (stronger for AG1478), while in A549, only AG1478 effectively inhibited the phosphorylation of Akt. Tyrphostins AG494 and AG1478 are ATP-competitors and are supposed to have a similar mechanism of action, but our results suggest that this is not quite true.

Abstract

We employed two selective EGFR tyrosine kinase inhibitors: AG494 (reversible) and AG1478 (irreversible) for growth regulation of human lung (A549) and prostate (DU145) cancer cell lines, cultured in chemically defined DMEM/F12 medium. Both tested tyrphostins significantly inhibited autocrine growth of the investigated cell lines. The action of AG494 was dose dependent, and at highest concentrations led to complete inhibition of growth. AG1478 seemed to be more effective at lower concentrations, but was unable to completely inhibit growth of A549 cells. Inhibition of EGFR kinase activity by AG494 in contrast to AG1478 had no effect on the activity of ERK in both cell lines. Both EGFR’s inhibitors induced apoptosis of the investigated lung and prostate cancer cell lines, but the proapoptotic effect of the investigated tyrphostins was greater in A549 than in DU145 cells. The tyrphostins arrested cell growth of DU145 and A549 cells in the G1 phase, similarly to other known inhibitors of EGFR. The influence of AG494 and AG1478 on the activity of two signaling proteins (AKT and ERK) was dependent upon the kind of investigated cells. In the case of DU145 cells, there was an evident decline in enzymatic activity of both kinases (stronger for AG1478), while in A549, only AG1478 effectively inhibited the phosphorylation of Akt. Tyrphostins AG494 and AG1478 are ATP-competitors and are supposed to have a similar mechanism of action, but our results suggest that this is not quite true.
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Keywords

epidermal growth factor (EGF); epidermal growth factor receptor (EGFR); tyrphostins; A549 cells; DU145 cells; autocrine growth regulation

About this article
Title

The effect of tyrphostins AG494 and AG1478 on the autocrine growth regulation of A549 and DU145 cells

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 50, No 2 (2012)

Pages

186-195

DOI

10.5603/FHC.2012.0028

Bibliographic record

Folia Histochem Cytobiol 2012;50(2):186-195.

Keywords

epidermal growth factor (EGF)
epidermal growth factor receptor (EGFR)
tyrphostins
A549 cells
DU145 cells
autocrine growth regulation

Authors

Agnieszka Bojko
Kinga Reichert
Anna Adamczyk
Joanna Ligęza
Janusz Ligęza
Andrzej Klein

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